Re: [NMusers] Numerical integreaion and change in clearance over time

From: Nick Holford <n.holford_at_auckland.ac.nz>
Date: Wed, 20 Dec 2017 17:58:16 +1300

Hi Paul,

Leonid has suggested some good methods for initial exploration of the
data so if you want to do a good job you can understand the magnitude of
the error using a short cut.

The real problem here seems to be poor time management planning. Data
does not arrive suddenly out of the blue without any warning with
decisions having to be made the next day.

Nick

On 20-Dec-17 14:52, Leonid Gibiansky wrote:
> One option is to run all analyses in analytical ADVANs and then re-run
> the final model in differential equations. If the results are close,
> it could be used as a justification of the final model. If not,
> differential equations solution should be preferred, I guess. In our
> experience, analytical solution is usually pretty close to the
> differential equations but this may depend on the data (time step of
> records). One option to increase precision is to place extra EVID=2
> records, so that the time step is smaller. Another option is to use
> MTIME for that, similar to:
>
> https://www.page-meeting.org/default.asp?abstract=1361
>
> Leonid
>
> On 12/19/2017 6:15 PM, Pavel Belo wrote:
>> Hello NONMEM Users,
>>
>> When clearance changes over time, the classic analytical solution for
>> the 2-compartment linear model is not correct. Nevertheless, if the
>> change is only ~30%, one can say it is still acceptable.  Time
>> required to run an analytical and numerical models is drastically
>> different, which can be important for decision making.  Did someone
>>  had an experience submitting using analytical solution when
>> clearance changes over time to an agency or a journal?  Can it be
>> acceptable?
>>
>> Thanks,
>>
>> Paul
>>
>

--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
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Received on Tue Dec 19 2017 - 23:58:16 EST

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